1. Field
This disclosure is concerned generally with the collection and separation of whole blood into useful components and specifically with a plastic blood bag system which permits a more dense centrifuged component in the lower part of the bag to be expressed to and out of the top of the bag.
2. Prior Art
Whole blood is commonly separated into its major components of less dense plasma and more dense red blood cells (RBCs) by first drawing the whole blood into a plastic bag known as a donor or primary bag. The bag contents are then centrifuged under controlled conditions to result in a lower, more dense portion of packed RBCs and an upper less dense plasma portion, which may be rich in platelets (platelet rich plasma or PRP).
The donor bag is typically connected via blood bag ports by plastic tubing to one or more satellite bags to form a "closed" system into which separated blood components (e.g., the PRP or RBCs) may be expressed by external manipulation and valves for further processing or use.
The above system for separating blood into its major components has remained generally unchanged since the 1950's when plastic blood bags were introduced commercially on a large scale.
In recent times, efforts have focused on preparing very specific "components" from whole blood (or fractionated plasma) so that if a patient needs a certain component (e.g., coagulation factors, albumin, platelets, ISG, RBCs, etc.), only that specific component can be administered. Although the system of this disclosure may be used to prepare other blood products, it is especially useful for preparing platelets.
The classical method of preparing platelet transfusion products from whole blood consists of an initial centrifugation of whole blood in a plastic blood bag at relatively low centrifugal force to separate most of the PRP from the red cells. The PRP is then commonly expressed into an attached satellite blood bag. This is followed by centrifugation of the PRP in the satellite bag at relatively high centrifugal force. This results in a lower sediment of platelets and an upper platelet poor plasma (PPP). The sedimented platelets are in the form of a pellet or "button" which is resuspended in a small volume of the PPP donor plasma (50-60 ml) to give the platelet concentrate (PC).
With good technique, about 2/3 of the platelets in a whole blood collection unit (about 450 ml.+-.10%) are recovered in the platelet concentrate. This is equivalent to about 8.times.10.sup.10 platelets per concentrate. However, achieving this yield of platelets requires strict attention to centrifugation protocols, frequent calibration of the centrifuges, and operator diligence. The fact that the minimum standard for platelet yield is only 5.5.times.10.sup.10 per concentrate attests to the operator-dependent nature of this procedure.
Recently, some transfusion services in Europe have begun to investigate and in some cases employ an alternate method of platelet preparation, specifically preparation from the "buffy coat" of centrifuged whole blood. In this procedure the initial centrifugation of whole blood is performed at relatively high centrifugal force to form three portions: an upper layer of relatively cell-free plasma, an intermediate "buffy coat" layer containing platelets and leukocytes, and a lower layer of red cells.
The intermediate buffy coat is separated and mixed with either a small volume of plasma (50-60 ml) or a synthetic medium. The mixture is then centrifuged at low centrifugal force to separate platelet concentrate (upper layer) from leukocytes (WBCs) and residual red cells. Data suggest that platelets prepared in this fashion are of improved quality, presumably because platelet activation that would otherwise occur during the pelleting step of the PRP centrifugation method is avoided.
The original work on buffy coat platelets was done at the Dutch Red Cross. Referred to as the Amsterdam method, it employed a standard quadruple multiple plastic bag system. After centrifugation of blood and removal of plasma from the main bag, the buffy coat layer was transferred to an empty connected satellite bag and then processed to platelet concentrate. Using this method, Pietersz et al., Vox Sang 1985; 49:81-85, found a mean of 7.2.times.10.sup.10 platelets per concentrate; the volume of blood collected in this study was about 500 Ml. Kretschmer et al., Infusionstherapie 1988; 15:232-239, found a mean of 6.3.times.10.sup.10 platelets per concentrate from 450 ml blood collections.
The Amsterdam method, while apparently giving respectable platelet yields, was cumbersome and labor-intensive. The buffy coat transfer step required the operator to massage the bag to prevent hang-up of the "sticky" buffy coat layer. These manipulations might influence platelet function and release of granulocyte enzymes. There was also no way to control the volume of buffy coat removed.
Other efforts to improve blood separation procedures or at least make it less burdensome are known. For example, U.S. Pat. No. 3,911,918 to Turner discloses a blood bag having an hour glass shape. That bag has a top portion for plasma, a bottom portion for RBCs and a middle portion for platelets and white blood cells. The hour glass shape is said to help position clamping or sealing devices at the juncture of the separated components after whole blood in the bag is centrifuged. This system has not been used on any significant commercial scale to date. See also U.S. Pat. No. 4,857,190 to Wada et al. showing a blood bag having a continuous but smaller receptacle adapted to help collect and define the interface of a centrifuged component.
In U.S. Pat. No. 4,608,178 to Johansson et al., there is disclosed a "top/bottom" bag in which the upper and lower portions of separated blood components can be simultaneously expressed from a specially designed bag which leaves behind in the bag the intermediate portion known as buffy coat. The expression of that system is controlled by a pressure plate on the bag and sensors which monitor the position of the intermediate layer such that it remains in the bag while the upper plasma is expressed from a top part and the lower red blood cells are expressed from a bottom part in the bag. Hence, the name top/bottom bag. The sensors in that system assure the simultaneous expression of the top and bottom components.
The above described systems are fairly recent and it is not clear yet whether those systems will in time replace existing blood separation systems based on the use of a relatively simple unmodified donor bag.
However, the systems do offer new ways to separate WBCs from platelets or to prepare platelets (contained in the intermediate or buffy coat portion). The patent to Johansson et al. show how to do this in a semi-automated manner. Hence, it potentially represents a semi-automated way to prepare platelets.
In an effort to overcome problems associated with the Amsterdam method, Johansson et al. developed the bag system with the top and bottom drainage of the primary bag and a sensor device which allowed partially automated blood separation. Kretschmer et al., cited above, used that type of system to prepare platelet concentrates from buffy coats and found a mean of 6.7.times.10.sup.10 platelets per unit.
In co-pending patent application Ser. No. 07/493,024 filed in the names of Carmen et al., there is disclosed another system for removing the lower contents of a blood bag in a relatively simple way. That system uses a tubular member which extends from an upper port into the interior of the bag, terminating just above the bag bottom. When pressure is applied to the bag, the lower contents of the bag exit through the tubular member and the top of the bag.
We are unaware of the use of longitudinal seals in any blood bag system which are made to facilitate removal of the lower contents of a blood bag through the top of the bag. In U.S. Pat. No. 4,619,650 to Wisdom, however, a blood bag with a different type of longitudinal seal is shown. Although the central longitudinal seal of that bag appears to leave a passageway between two halves of the bag at the top (not the bottom) that bag would not allow the lower contents of the bag to be removed from the top of the bag as in the present system. More over, the purpose of the seal in that bag is to provide a line along which the bag can be torn open for the efficient removal (via machine) of frozen plasma.
Although the above system has been found useful and may be a practical alternative to the top-bottom bag, we have now found what may be an even more practical alternative which uses a novel blood bag construction that offers surprising manufacturing and use advantages. Details of the system are described below.